Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals and environmental conditions:

Rats were obtained from Charles River Deutschland GmbHAnimals were a minimum of 8 weeksof age at delivery. Males were 309-377 grams and females were 204-248 grams. Animals were acclimated for 7 days prior to treatment, under test conditions with an evaluation of the health status. Animals rooms were air conditioned with 10-15 air changes per hour; the environment was monitored continously with recordings of temperature and relative humidity, 12 hours artificial fluorescent light/12 hours dark with background music played at a centrally defined low volume for at least 8 hours during the light period. Animals were housed in Makrolon (R) cages with wire mesh tops and standard granulated softwood bedding. Pelleted standard rat/mouse maintenance diet was available ad libitum. Tap water from Fullinsdorf in bottles was available ad libitum.

Administration / exposure

Route of administration:

inhalation

Type of inhalation exposure (if applicable):

whole body

Vehicle:

unchanged (no vehicle)

Details on exposure:

The vapor generation system consisted of a round bottomed flask that was placed in a heating device set at 30 °C. Compressed air was supplied into the glass flasks and allowed the liquid test item to equilibrate with the temperature of the walls of the container. The vapor produced passed through a pipe and was then mixed and diluted with filtered air and conveyed to the inlet of the whole-body exposure chamber. After set-up of the definitive generation system the chamber concentration and stability of CPTMO over the duration of 6 hours was determined on two occasions prior to the start of the animal exposures.

Details on mating procedure:

During the pairing period, rats were housed overnight with one male and one female in Makrolon pairing cages. The femlae was placed with the same male until mating occurred or two weeks elapsed.

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

The nominal atmosphere concentration was determined once daily by weighing the test item container before and after each exposure. The weight of the test item used was divided by the total air flow volume to give the nominal concentration. The test atmosphere concentration in each chamber was determined daily, 5 times per hour per chamber during each hour of exposure.

Duration of treatment / exposure:

Exposure period: 28 days Premating exposure period (males): 14 days Premating exposure period (females): 14 days Duration of test: until the individual day 19 post coitum

(3-Chloropropyl)trimethoxysilane was administered for 6 hours daily by whole-body vapour inhalation to male rats for 28 days and to female rats throughout the 14-day pre-pairing, pairing and gestation period until the individual day 19 post coitum.

Frequency of treatment:

daily

Details on study schedule:

Premating exposure period (males): 14 daysPremating exposure period (females): 14 daysDuration of test: until the individual day 19 post coitum

(3-Chloropropyl)trimethoxysilane was administered for 6 hours daily by whole-body vapour inhalation to male rats for 28 days and to female rats throughout the 14-day pre-pairing, pairing and gestation period until the individual day 19 post coitum.

Doses / concentrations

Remarks:

Doses / Concentrations:0, 5, 25 and 100 ppmBasis:nominal conc.

No. of animals per sex per dose:

10/sex/dose

Control animals:

yes, concurrent no treatment

Details on study design:

The animals were exposed to the following mean test item concentrations: Group 1: 0 ppm (air control) Group 2: 5 ppm Group 3: 25 ppm Group 4: 100 ppm Control animals were exposed to air only under the same conditions as animals exposed to the test item. P generation males were sacrificed after they had been treated for 28 days, P generation females and pups were sacrificed on day 4 post partum.

Examinations

Parental animals: Observations and examinations:

Animals were observed twice daily for mortalities and clinical signs. Detailed clinical observations were performed once per week. A Functional Observational battery (modified Irwin screen test) was performed once during the test (males: shortly before sacrifice; females: on day 3 post-partum). Body weights and food consumption was recorded.

Litter observations:

The litters were examined for litter size, live birth, stillbirth and any gross anomalies. The sex ratio of the pups were recorded. Pups were weighed individually on day 0, 1 and 4 post partum. The pups were observed daily for survival and behavioral abnormalities in nesting and nursing. Dead pups and pups killed on day 4 post partum were examined macroscopically.

Postmortem examinations (parental animals):

Parental generation males were sacrificed after they had been treated for 28 days, Parental generation females were sacrificed on day 4 post partum.A complete gross necropsy was performed on all adult animals.ORGAN WEIGHTS From all adult males and females the following organs were taken, trimmed and weighed: liver, heart, adrenals*, overies*, thymus, uterus, kidneys*, testes*, spleen, epididymides*, seminal vesicles, with coagulating glands and their fluids(as one unit), lungs, prostate, brain * = paired weights TISSUE PRESERVATION The following tissues were collected from all adult males and females and preserved in neutral phosphate buffered 4% formaldehyde solution (except for testes and epididymides, which were fixed in Bouin's fixative): gross lesions, uterus, heart, brain, thymus, spinal cord, thyroid, small and large intestines (incl. Peyers Patches), trachea and lungs (preserved by inflation with fixative and then immersion), stomach, urinary bladder, liver, lymph nodes (mediastinal and mesenteric), kidneys, sciatic nerve, adrenals, bone marrow, spleen, testes, ovaries, epididymides, uterus, prostate, seminal vesicles with coagulation glands Full histopathology was carried out on the preserved organs and tissues of the control and high dose group animals.Examinations were extended to lower dose group animals if treatment related changes were seen in the high dose group. For perganant females, the number of corora lutea and the number of impantation sites were recorded. Mated females that did not deliver were sacrificed on gestation day 24-27. Histological exam of ovaries and uterus was carried out onany females that did not give birth. Microscopic exam of the reproductive organs of all infertile males was made if necessary.

Postmortem examinations (offspring):

Pups were sacrificed on day 4 post partum.The litters were examined for litter size, live birth, stillbirth and any gross anomalies.

Statistics:

Statistical Methods: Mean and standard deviation of data were calculated. Univariate one-way analysis of variance was used to assess the significance of intergroup differences. If the variables were assumed to follow a normal distribution, the Dunnett t-test, based on a pooled variance estimate, was used for intergroup comparisons. The Steel test (rank test) was applied when the data could not be assumed to follow a normal distribution. Fisher's Exact test for 2x2 tables was applied if the variables could be dichotomized without loss of information.

Abnormal findings at first litter check and during lactation to weaningSex ratiosPup weights to day 4 post partum

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Details on results (P0)

The fertility rate was high resulting in at least 9 litters per group for evaluation of reproduction data. At all concentrations, there were no treatment-related effects on precoital time, fertility indices, mean duration of gestation, number of implantations, post-implantation loss through to scheduled sacrifice on day 4 post partum. The mean number of corpora lutea per dam (determined at necropsy) was similar in all groups and gave no indication of a test item-related effect. There were no findings, which distinguished test item-treated animals from controls. In particular, no treatment-related histopathological findings were observed in the reproductive organs of either sex from the parental generation. The assessment of the integrity of the spermatogenetic cycle did not provide any evidence of impaired spermatogenesis.

Effect levels (P0)

Dose descriptor:

NOAEC

Effect level:

100 ppm (nominal)

Sex:

male/female

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Histopathological findings:

not examined

Details on results (F1)

At all concentrations, there were no treatment-related effects on pup survival or litter size from birth through to scheduled sacrifice on day 4 post partum.

No abnormal findings were noted for pups at first litter check or during the first 4 days post partum. Sex ratios at first litter check and on day 4 post partum were unaffected by treatment with the test item. Mean pup weights on day 0 and day 1 post partum were unaffected by treatment with the test item. Mean pup weight development during the first 4 days post partum lactation was unaffected by treatment with the test item.

Effect levels (F1)

Dose descriptor:

NOAEC

Generation:

F1

Effect level:

100 ppm (nominal)

Sex:

male/female

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Exposure to (3-Chloropropyl)trimethoxysilane up to and including the high concentration of 100 ppm did not result in any signs of general or reproductive toxicity of the test item. Based on these results the NOEC (no observed effect concentration) was established at 100 ppm.

Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.

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